Treatment of Ovarian Hypers timulation Syndrome inA Mouse Model by Cannabidiol, An Angiogenesis PathwayInhibitor

Background: Prevention of ovarian hypers timulation syndrome(OHSS) is possible with pharmacological and non-pharmacologicalmethods. Non-pharmacological methods includereducing ovarian s timulation, reducing hCG β dose, delayinghCG β or coas ting injection, canceling the cycle, freezing thefetus for replacement at a later time, follicular aspiration, andoocyte verification. However, commercially available VEGFreducingdrugs now have side effects that preclude their useas a treatment for OHSS in young women; for this reason, researchersare looking at new drugs to treat OHSS. Cannabinoids(CBD) are the active ingredient in hemp (Cannabis sativaL) and are the mos t important source of phytocannabinoids. Ithas no psychoactive effect and modulates the activity of CB۱and CB۲ receptors, and is involved in regulating female reproductiveprocesses such as proliferation, pain modulation andimproving the path of angiogenesis. CBD affects the hypothalamic-pituitary-ovarian axis and affects the secretion of s teroidhormone. In OHSS, androgens cause proliferation of the thecainterna and granulosa and increase AMH, upsetting the balanceof the proliferation pathway. Because CBD inhibits cell proliferationand migration. Therefore, in this s tudy, we use CBD toimprove OHSS in this s tudy. Our aim was to inves tigate the roleof CBD in the pathophysiology of OHSS and its use to modulatethe pathway of angiogenesis and the VEGF gene.Materials and Methods: This s tudy was a basal genomic levelsanalysis in the OHSS-induced model, which used ۳۲ NMRImice. Thirty-two female immature NMRI rats were randomlyassigned to four groups. The control group (n = ۸) receivedsaline only for four consecutive days. The remaining twentyfourrats received ۱۰ IU of pregnant mare serum gonadotropin(PMSG) followed by ۳۰ IU of human chorionic gonadotropin (hCG) to induce OHSS. Group ۲ (n = ۸) was managed withno additional intervention after the induction of OHSS. Group۳ (n = ۸) received ۳۲nmol DMSO ۲ hours before the PMSGinjection for four consecutive days and ۲ hours before the hCGinjection on the fourth day. Group ۴ (n = ۸) received ۳۰ mg/kgCBD after induction of OHSS, respectively. CBD was administered ۲ hours before the PMSG injection for four consecutivedays and ۲ hours before the hCG injection on the fifth day.Body and ovary weight, vascular permeability (VP), and levelsof VEGF in the blood serum were examined in all animals.Results: CBD Reduced Body Weight, Ovary Weight, and VPCompared to that of the OHSS group (P<۰.۰۵). VEGF expressionin ovaries and peritoneal VEGF levels were decreased inthe CBD group compared to that of the OHSS group (P<۰.۰۵).Conclusion: CBD was active in the alleviation of OHSSthrough suppression of VEGF and VP. Overall, we concludethat CBD is effective in the downregulation of VEGF and improvementin vascular permeability in OHSS.

کلیدواژه ها:

Animal Model ، Cannabidiol ، Ovarian hypers timulationSyndrome ، VEGF